Daily Gentamicin Research Articles

Impact of once-daily versus multiple-daily dosing of gentamicin on the incidence of acute kidney injury in patients treated with synergistic combinations of antibiotics

BackgroundGentamicin is a commonly used antibiotic with synergistic effects that is administered once or multiple times daily. However, the influence of the daily administration frequency on renal function has not yet been identified. This study aimed to investigate the effect of the daily dosing frequency on worsening renal function in patients receiving gentamicin.MethodsThis study included 35 patients undergoing gentamicin treatment who had at least one serum trough level measured and underwent therapeutic drug monitoring (TDM). We evaluated the influence of daily dosing frequency on gentamicin trough concentration and the risk of acute kidney injury (AKI).ResultsCompared to patients who received gentamicin once-daily dosing (n = 22), patients who received multiple-daily dosing (n = 13) had significantly higher initial and minimum trough concentrations after TDM. The proportion of patients with trough concentrations lower than 1.0 µg/mL was significantly higher in the once-daily dosing group at the initial trough concentration, whereas there was no significant difference at the minimum trough concentration after TDM. AKI developed in nine patients; however, there was no significant difference in the incidence of AKI according to the frequency of daily gentamicin dosing. In contrast, a higher minimum trough concentration after TDM was found to be a risk factor for AKI development with an odds ratio of 9.2 (95% confidence intervals; 1.3–65.5).ConclusionA higher trough concentration of gentamicin correlated with a higher incidence of AKI. The risk of developing AKI may be reduced by choosing a once-daily dosing regimen or implementing TDM.

Protective Effect of Neutral Electrolyzed Saline on Gentamicin-Induced Nephrotoxicity: Evaluation of Histopathologic Parameters in a Murine Model.

Background and Objectives: Gentamicin (GM) is a nephrotoxic aminoglycoside. Neutral electrolyzed saline (SES) is a compound with anti-inflammatory, antioxidant, and immunomodulatory properties. The objective of the present study was to evaluate whether kidney damage by GM can be prevented and/or reversed through the administration of SES. Materials and Methods: The study was carried out as a prospective, single-blind, five-arm, parallel-group, randomized, preclinical trial. The nephrotoxicity model was established in male BALB/c mice by administering GM at a dose of 100 mg/kg/day intraperitoneally for 30 days, concomitantly administering (+) SES or placebo (physiologic saline solution), and then administering SES for another 30 days after the initial 30 days of GM plus SES or placebo. At the end of the test, the mice were euthanized, and renal tissues were evaluated histopathologically. Results: The GM + placebo group showed significant tubular injury, interstitial fibrosis, and increased interstitial infiltrate of inflammatory cells compared with the group without GM. Tubular injury and interstitial fibrosis were lower in the groups that received concomitant GM + SES compared with the GM + placebo group. SES administration for 30 days after the GM administration periods (GM + placebo and GM + SES for 30 days) did not reduce nephrotoxicity. Conclusions: Intraperitoneal administration of SES prevents gentamicin-induced histologic nephrotoxicity when administered concomitantly, but it cannot reverse the damage when administered later.

Prospektives Audit des Gentamicin Drug Monitorings in einem Kinderkrebszentrum

Many pediatric cancer centers still use Gentamicin as first line combination treatment in patients with fever and neutropenia. Since 2011, our center has implemented a dosing regimen with 250 mg/m2 BSA (max. 10 mg/kg, max. 400 mg) as a single daily infusion according to the German guideline. In this prospective audit (February 2011 to December 2019), 105 Gentamicin treatment cycles were analyzed in 66 pediatric cancer patients, focusing on adherence to the dosing regimen and the drug monitoring results. Adherence to the dosing regimen was high (89%). In 64% of all cycles, the Cmax (drawn 1 h after the 2nd dose) reached the target of 10-20 µg/ml. Cmax significantly correlated with dosing in mg/m2 BSA (p=0,007), but not with dosing in mg/kg (p=0,366). Age below 6 years did not influence these results. The Gentamicin Ctrough (drawn 8-10 h after the second dose) was < 2 µg/ml in 93% of all cycles without any dose correlation. None of the patients experienced Gentamicin-associated nephrotoxicity. This prospective audit of single daily infusion Gentamicin in pediatric cancer patients without impaired renal function elicits the feasibility and safety of the dosing regimen in mg/m2 BSA according to the German guideline. Since indications for first-line gentamicin are limited, a multicenter prospective study would be advantageous to confirm these observations.

Chlorhexidine-impregnated sponge dressing for prevention of catheter exit-site infection in peritoneal dialysis patients: a pilot study.

The study aimed to examine effect of chlorhexidine dressing in the prevention of peritoneal dialysis (PD)-related infection in PD patients. This single-center pilot study recruited 50 incident PD patients to use weekly chlorhexidine dressing. The primary outcome was exit-site/tunnel infection rate. Secondary outcomes were peritonitis rate, time to first PD-related infection, infection-related hospitalization, technique and patient survival, adverse events, and chlorhexidine dressing acceptability. These clinical outcomes were compared with those of a historical cohort (2016-2017) using daily gentamicin cream. A total of 50 patients were recruited to use chlorhexidine and followed up for one year. The exit-site/tunnel infection rate was 0.09 (95% confidence interval [CI] 0.02-0.22) and peritonitis rate was 0.07 (95% CI 0.01-0.19) episodes per patient-year with chlorhexidine dressing. The 1-year infection-free survival rates for exit-site/tunnel infection and peritonitis were 92% and 94%, respectively. The 1-year technique and patient survival rates were 86% and 96%, respectively. Overall, 12% of participants developed localized contact dermatitis with chlorhexidine. Most participants (73%) reported that chlorhexidine dressings were very acceptable. Compared to a historical cohort using gentamicin cream (n = 238), the chlorhexidine group had similar exit-site/tunnel infection rates (incidence rate ratio [IRR] 0.65, 95% CI 0.22-1.92) but had lower peritonitis rates (IRR 0.24, 95% CI 0.07-0.77), and lower PD infection-related hospitalization rates (IRR 0.21, 95% CI 0.06-0.69) after adjusting for age, sex, race, primary kidney disease, and diabetes mellitus. Weekly chlorhexidine dressing was associated with acceptable PD-related infection outcomes and was well-accepted by patients, although had a 12% rate of delayed localized contact dermatitis. The study was registered under www.clinicaltrials.gov with the reference number of NCT03406520 on 23 January 2018.

Pirfenidone attenuates gentamicin-induced acute kidney injury by inhibiting inflammasome-dependent NLRP3 pathway in rats

Acute kidney injury (AKI) is an abrupt and usually reversible decline in renal function. AKI is considered one of the main drawbacks of the use of gentamicin that critically limits its clinical use. In this study, pirfenidone, an oral antifibrotic drug, was given to rats (200 mg/kg, p.o., daily) for seven days alone before the initiation of gentamicin treatment and continued for seven days alongside daily gentamicin injections. In gentamicin group, gentamicin was given to Wistar rats (100 mg/kg, i.p., daily) for seven days to induce AKI. Pirfenidone managed to alleviate gentamicin-induced AKI by improving kidney function parameters including serum creatinine, blood urea nitrogen (BUN), proteinuria, relative kidney-to-body weight ratio and creatinine clearance. Pirfenidone decreased cytotoxicity induced by gentamicin by decreasing lactate dehydrogenase (LDH) activity and improving histologic picture of tubules and glomeruli. Pirfenidone also alleviated oxidative stress induced by gentamicin by reducing malondialdehyde (MDA) and elevating reduced glutathione (GSH). Pirfenidone prevented the upregulated inflammasome pathway markers in the kidney. It succeeded in decreasing toll like recpetor-4 (TLR4), nuclear factor-kappa B (NF-κB), nucleotide-binding oligomerization domain [NOD]-like pyrin domain containing protein 3 (NLRP3), caspase-1, interleukin-1β (IL-1β) and IL-18 levels. Additionally, Pirfenidone caused a decrease in macrophage infiltration displayed by reduction in renal monocyte chemoattractant protein-1 (MCP-1) levels. To sum up, pirfenidone can effectively mitigate gentamicin-induced AKI by inhibiting oxidative stress, macrophage infiltration and inflammasome-dependent NLRP3 pathway-induced inflammation.

P1204PHROPHYLATIC GENTAMICIN - A THERAPEUTIC WEAPON IN THE COMBAT OF EXIT SITE INFECTIONS IN PERITONEAL DIALYSIS

Abstract Background and Aims Infection-related complications, such as exit-site infection (ESI) and peritonitis, are one of the main causes of technique failure and dropout in patients under peritoneal dialysis. Several studies have demonstrated the positive effect of daily topical antibiotics (AB) in preventing ESI. The aim of this study is to demonstrate the impact of topical gentamicin (TG) in preventing ESI, between 2009 and 2019, in a single-center of a medium-sized hospital in Portugal. Method Descriptive and retrospective analysis was performed. Demographic data, comorbidities, type of catheter placement and PD prescription were collected. For each patient, it was determined the time free of prophylactic AB (NTG) and under topical gentamicin (ophthalmic formula, once a day, applied on exit site). ESI cases were identify. Results Eighty-five patients were included, with a mean age of 53.2 ± 14.6 years; 69.5% were male. Cardiovascular comorbidities, like arterial hypertension and diabetes, were highly prevalent (88.2% and 76.5% respectively). Chronic glomerulonephritis and diabetes were the main causes of CKD (19; 22.4%; 15; 17.6%). More than 80% of the patients had previous Nephrology follow up. Percutaneous approach was the first option to catheter placement in 70.6% of the cases and DPA was performed in 53,0%. Every patient started the PD program free of prophylactic AB (n=85); 35 patients started TG at some point. Forty episodes of ESI were recorded, 39 (97.5%) in the NTG group. Staphylococcus aureus was the most frequently identified organism (16; 41.0%), followed by Staphylococcus epidermis (5; 12.5%) and Corynebacterium (5; 12.5%). The Kaplan-Meier analysis demonstrated that patients in TG were associated with better free-time of first peritonitis ((705 vs 985 days; p=0.001). The multivariate Cox regression model confirmed a 14 times higher risk of ESI in NTG group (HR 14.4; 95% CI 1.97-105.45; p=0.001). Conclusion Although mupirocin is still the first option in many centers, some studies have demonstrated a benefic role of gentamicin in reducing ESI, not only by Pseudomonas species but also Staphylococcus aureus. The results of our study confirmed that topical daily gentamicin is highly effective preventing ESI in PD patients. Despite of the concern with the gentamicin-resistant infections, just one patient developed ESI under gentamicin, and the identified microorganism was the Staphylococcus epidermidis.

Interest of therapeutic drug monitoring of aminoglycosides administered by a monodose regimen

BackgroundAlthough the once-daily regimen of aminoglycosides (AG) is considered as predominantly used by many centers, the level of evidence of Therapeutic Drug Monitoring (TDM) of AG in cases of once-daily has not been clearly defined. The objective of this study is to evaluate the impact of TDM in achievement or maintaining target serum concentrations in patients receiving once-daily administration of AG. MethodsWe performed a retrospective analysis of data from patients having received a once daily amikacin or gentamicin and underwent routine TDM. A longitudinal follow up was performed. Data were analyzed according to the adhesion or not to recommendations. A logistic regression was performed in order to evaluate the effect of covariates (age, gender, weight, creatinine clearance [CLcr], TDM-based dose adjustment, weighted dose of AG) on the achievement of non-toxic Cmin. ResultsA total 437 blood samples issued from 324 patients were analyzed. The cut-off value of Clcr associated with a risk of toxic Cmin was≤41.66mL/min (OR: 11.29; 95%CI: 7.21–17.61; P<0.0001). Eighty-eight patients (27.1%) have at least two sampling points. The univariate analysis showed that the age, weight, CLcr and TDM-based dose adjustment were found to be significant factors in the achievement of non-toxic Cmin. In multivariate analysis, only TDM-based dose adjustment remains a significant factor in the achievement of non-toxic Cmin (OR: 6.66; 95%CI: 2.26–19.63; P=0.0006). ConclusionOur study demonstrates the usefulness of TDM-based dosing adjustment of AG antibiotics in achieving nontoxic trough concentrations, particularly in critically ill patients, as they are prone to a renal impairment.

Neomycin-polymyxin or gentamicin bladder instillations decrease symptomatic urinary tract infections in neurogenic bladder patients on clean intermittent catheterization

Recurrent urinary tract infections (UTIs) are common in patients with neurogenic bladder (NGB) performing clean intermittent catheterization (CIC)treated with or without oral antibiotic prophylaxis. The authors aim to determine if daily neomycin-polymyxin or gentamicin bladder instillations reduce the rate of symptomatic UTIs, the need for oral antibiotic prophylaxis, emergency department (ED) visits for UTI, and inpatient hospitalizations for UTI in patients with NGB on CIC. The authors also aim to investigate resistance patterns in urine microorganisms in patients treated with antibiotic bladder instillations. The authors retrospectively reviewed the records of all-age patients cared for in the pediatric urology clinic with NGB on CIC having symptomatic UTIs and on daily intravesical instillations of neomycin-polymyxin or gentamicin between 2013 and 2017. Symptomatic UTIs were defined as a positive urine culture with greater than 10,000 colony forming units/mL associated with one or more of the following patient complaints: cloudy/foul-smelling urine, fevers, chills, increase in bladder spasms, pain, urinary leakage, or physician decision for antibiotic treatment. Multidrug-resistant organisms were resistant to two or more classes of antibiotics. Fifty-two patients with a median age of 14.5 years and 192 distinct urine cultures were identified. 90.4% and 9.6% of patients received neomycin-polymyxin and gentamicin instillations, respectively. After initiation of intravesical antibiotics, the rate of symptomatic UTIs was reduced by 58% (incidence rate ratio [IRR]: 0.42, 95% confidence interval [CI]: 0.31-0.56; P<0.001), the rate of ED visits was reduced by 54% (IRR: 0.46, 95% CI: 0.30-0.71; P<0.001), and the rate of inpatient hospitalizations for UTI was reduced by 39% (IRR: 0.61, 95% CI: 0.37-0.98; P=0.043). Fewer patients received oral antibiotic prophylaxis after initiation of antibiotic instillations (odds ratio: 0.12, 95% CI: 0.02-0.067; P=0.016). There was a trend towarda decrease in multidrug resistance and no change in gentamicin resistance in urine microorganisms. This study describes a feasible alternative treatment for patients with NGB on CIC who have persistent UTIs despite oral antibiotic prophylaxis, and for some patients, it may suggest a possibility of discontinuing oral prophylaxis. Limitations include a retrospective design with a small cohort of patients and varying dosages of neomycin-polymyxin. Antibiotic bladder instillations appear to decrease frequency of symptomatic UTIs, ED visits for UTI, inpatient hospitalizations for UTI, and the need for oral antibiotic prophylaxis in patients with NGB on CIC. There was no increase in multidrug resistance or gentamicin resistance in UTI organisms with use of intravesical antibiotic instillation.

Daily gentamicin using ideal body weight demonstrates lower risk of postpartum endometritis and increased chance of successful outcome compared with traditional 8-hour dosing for the treatment of intrapartum chorioamnionitis

Background: Clinical chorioamnionitis complicates approximately 1–4% of pregnancies overall. Although universal agreement does not exist regarding the antibiotic regimen of choice, most studies have evaluated intravenous ampicillin dosed at 2 g every 6 hours plus gentamicin dosed every 8 hours. Only three studies have examined daily gentamicin for the treatment of intrapartum chorioamnionitis and thus is insufficiently investigated.Objective: This study seeks to determine whether daily dosing of gentamicin using ideal body weight for the treatment of intrapartum chorioamnionitis is more or equivalently efficacious when compared to traditional 8-hour dosing regimens.Materials and methods: We conducted a retrospective cohort study and reviewed charts on all women receiving treatment for intrapartum chorioamnionitis, which included intravenous gentamicin daily dosing calculated using 5 mg/kg ideal body weight or receiving traditional every 8 hours dosing of gentamicin at two large academic centers. Our primary outcomes were resolution of infection following delivery without the development of maternal endometritis and/or neonatal sepsis. Baseline characteristics were compared between dosing groups using Welch two-sample t-tests for continuous variables, uncorrected X2 test and exact binomial 95% confidence intervals. We calculated the risk ratios of each outcome in the ideal versus traditional dosing groups using modified Poisson regression, both crude and adjusted. Adjusted models were controlled for variables determined to be potential confounders, which included BMI, diabetes mellitus, gestational blood pressure >140/90, group β-Streptococcus status, race, advanced maternal age (>34 y), and parity.Results: The study included 500 patients with 255 patients receiving daily dosing of gentamicin and 245 receiving traditional dosing of gentamicin. Of the patients receiving daily gentamicin compared to traditional dosing, 95.7% (95% CI 94.9–96.6%) achieved the primary outcome versus 92% (95% CI 90.8 − 93.2%), 2.4% (95% CI 1.8–3%) developed endometritis versus 5.6% (4.5–6.7%), 1.6% (95% CI 1.1–2.1%) delivered neonates with sepsis versus 3.3% (CI 2.5–4.1%), and 36.9% required cesarean delivery versus 41.4%. In crude analysis, compared to traditional dosing, IDW daily dosing was associated with a lower risk of postpartum endometritis (RR 0.42, 95% CI 0.16–1.10, p = .032). After adjusting for BMI, diabetes mellitus, gestational blood pressure >140/90, group β-Streptococcus status, race, advanced maternal age (>34 y), and parity, the IDW daily dosing group had a 5% greater chance of successful outcome (RR 1.05, 95% CI 1.00–1.10, p = .046) and a 64% lower risk of endometritis (RR 0.35, 95% CI 0.15–0.83, p = .017).Conclusion: Daily dosing of gentamicin using ideal body weight is associated with a lower risk of postpartum endometritis and high chance of a successful outcome in the treatment of intrapartum chorioamnionitis compared with traditional 8-hour dosing in our ethnically diverse, urban population and thus may be considered a superior option to every 8 hours dosing regimens.

One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates: Updated Cochrane Review

One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates: Updated Cochrane Review

Nebulized Gentamicin as an Alternative to Nebulized Tobramycin for Tracheitis in Pediatric Patients.

Tracheitis is an infection of the lower respiratory tract and is defined by the US Centers for Disease Control and Prevention (CDC) based on signs and symptoms with no radiographic evidence of pneumonia. One method of treatment involves the use of tobramycin given by nebulizer. The purpose of this study was to compare the safety and efficacy of nebulized gentamicin with nebulized tobramycin. This study was conducted in patients under 21 years of age who received greater than or equal to 1 day of gentamicin, 80 mg, or tobramycin, 300 mg, given twice a day by nebulization within the 14-month study period. The primary endpoint was amount of time until the patient no longer met the CDC definition of tracheitis. There were 19 patients who presented with 60 separate encounters. The average age of the patients within the gentamicin group was 7.2 and 5 years old within the tobramycin group. The average duration of time for the gentamicin treatment encounters to be free of the CDC definition of tracheitis was 3.36 days compared to 3.17 days with tobramycin. No adverse effects were observed that were attributable to aminoglycoside nebulization. No differences were detected between the safety and efficacy of intravenous gentamicin administered twice a day by nebulizer and that of tobramycin inhalation solution given twice daily in children without cystic fibrosis.

One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates.

Animal studies and trials in older children and adults suggest that a 'one dose per day' regimen of gentamicin is superior to a 'multiple doses per day' regimen. To compare the efficacy and safety of one dose per day compared to multiple doses per day of gentamicin in suspected or proven sepsis in neonates. Eligible studies were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 3) in the Cochrane Library (searched 8 April 2016), MEDLINE (1966 to 8 April 2016), Embase (1980 to 8 April 2016), and CINAHL (December 1982 to 8 April 2016). All randomised or quasi-randomised controlled trials comparing one dose per day ('once a day') compared to multiple doses per day ('multiple doses a day') of gentamicin to newborn infants. Data collection and analysis was performed according to the standards of the Cochrane Neonatal Review Group. Eleven RCTs were included (N = 574) and 28 excluded. All except one study enrolled infants of more than 32 weeks' gestation. Limited information suggested that infants in both 'once a day' as well as 'multiple doses a day' regimens showed adequate clearance of sepsis (typical RR 1.00, 95% CI 0.84 to 1.19; typical RD 0.00, 95% CI -0.19 to 0.19; 3 trials; N = 37). 'Once a day' gentamicin regimen was associated with fewer failures to attain peak level of at least 5 µg/ml (typical RR 0.22, 95% CI 0.11 to 0.47; typical RD -0.13, 95% CI -0.19 to -0.08; number needed to treat for an additional beneficial outcome (NNTB) = 8; 9 trials; N = 422); and fewer failures to achieve trough levels of 2 µg/ml or less (typical RR 0.38, 95% CI 0.27 to 0.55; typical RD -0.22, 95% CI -0.29 to -0.15; NNTB = 4; 11 trials; N = 503). 'Once a day' gentamicin achieved higher peak levels (MD 2.58, 95% CI 2.26 to 2.89; 10 trials; N = 440) and lower trough levels (MD -0.57, 95% CI -0.69 to -0.44; 10 trials; N = 440) than 'multiple doses a day' regimen. There was no significant difference in ototoxicity between two groups (typical RR 1.69, 95% CI 0.18 to 16.25; typical RD 0.01, 95% CI -0.04 to 0.05; 5 trials; N = 214). Nephrotoxicity was not noted with either of the treatment regimens. Overall, the quality of evidence was considered to be moderate on GRADE analysis, given the small sample size and unclear/high risk of bias in some of the domains in a few of the included studies. There is insufficient evidence from the currently available RCTs to conclude whether a 'once a day' or a 'multiple doses a day' regimen of gentamicin is superior in treating proven neonatal sepsis. However, data suggest that pharmacokinetic properties of a 'once a day' gentamicin regimen are superior to a 'multiple doses a day' regimen in that it achieves higher peak levels while avoiding toxic trough levels. There was no change in nephrotoxicity or auditory toxicity. Based on the assessment of pharmacokinetics, a 'once a day regimen' may be superior in treating sepsis in neonates of more than 32 weeks' gestation.

DEVELOPMENT OF A ONCE DAILY GENTAMICIN REGIMEN FOR PAEDIATRIC SURGERY PATIENTS

AimIntravenous gentamicin is given as a 5 day course to paediatric patients who have undergone abdominal surgery. There was an impression that the multiple daily dosing regimen in use at...

ONCE DAILY GENTAMICIN DOSE BANDING IN NEWBORNS WITH SIGNS OF EARLY ONSET OF NEONATAL SEPSIS (EONS), BASED ON INITIAL BIRTH WEIGHT AND GESTATIONAL AGE

AimProspective assessment of safety of dose banding of once daily gentamicin in newborns with signs of EONS in their first days of life.MethodAll neonates admitted on the level-3 neonatal unit,...

Long-Term Exit-Site Gentamicin Prophylaxis and Gentamicin Resistance in a Peritoneal Dialysis Program.

♦ Daily gentamicin cream exit-site prophylaxis reduces peritoneal dialysis (PD)-related gram-negative infections. However, there is a concern about the potential for increasing gentamicin resistance with the long-term use of prophylactic gentamicin. This study evaluated the incidence of gentamicin-resistant PD-related infections over more than 2 decades. ♦ Study data on prevalent PD patients were retrieved from a prospectively maintained institutional review board (IRB)-approved PD registry at a single center from January 1, 1991, to December 31, 2000, and January 1, 2004, to December 31, 2013. The rates of gram-negative infections, fungal infections and those infections with organisms resistant to gentamicin were examined for the 2 periods. Period 1 from 1991 to 2000 when S. aureus prophylaxis consisted initially of oral rifampin to treat nasal carriage with S. aureus, and was then daily exit-site mupirocin ointment for all PD patients, was compared to the period from 2004 to 2013 when daily exit-site gentamicin cream was prescribed as prophylaxis (Period 2). ♦ The study included a total of 444 PD patients (265 and 179 in Period 1 and Period 2, respectively). No significant difference was noted in demographics between the 2 periods except race. The gram-negative exit-site infection rates for Period 1 and Period 2 were 0.109 versus 0.027 (p < 0.0001). Gram-negative peritonitis rates were similar. There were 3 episodes of gentamicin-resistant infections in each period. Fungal infections remained consistently low. ♦ Despite a decade of exit-site gentamicin prophylaxis, gentamicin-resistant PD-related infections and fungal infections remained very low and similar to the prior period.

Full-thickness porcine burns infected with Staphylococcus aureus or Pseudomonas aeruginosa can be effectively treated with topical antibiotics.

Burn and blast injuries are frequently complicated by invasive infections, which lead to poor wound healing, delay in treatment, disability, or death. Traditional approach centers on early debridement, fluid resuscitation, and adjunct intravenous antibiotics. These modalities often prove inadequate in burns, where compromised local vasculature limits the tissue penetration of systemic antibiotics. Here, we demonstrate the treatment of infected burns with topical delivery of ultrahigh concentrations of antibiotics. Standardized burns were inoculated with Staphylococcus aureus or Pseudomonas aeruginosa. After debridement, burns were treated with either gentamicin (2 mg/mL) or minocycline (1 mg/mL) at concentrations greater than 1,000 times the minimum inhibitory concentration. Amount of bacteria was quantified in tissue biopsies and wound fluid following treatment. After six days of gentamicin or minocycline treatment, S. aureus counts decreased from 4.2 to 0.31 and 0.72 log CFU/g in tissue, respectively. Similarly, P. aeruginosa counts decreased from 2.5 to 0.0 and 1.5 log CFU/g in tissue, respectively. Counts of both S. aureus and P. aeruginosa remained at a baseline of 0.0 log CFU/mL in wound fluid for both treatment groups. The findings here demonstrate that super-therapeutic concentrations of antibiotics delivered topically can rapidly reduce bacterial counts in infected full-thickness porcine burns. This treatment approach may aid wound bed preparation and accelerate time to grafting.

Effect of sepsis and systemic inflammatory response syndrome on neonatal hearing screening outcomes following gentamicin exposure

ObjectivesHearing loss in neonatal intensive care unit (NICU) graduates range from 2% to 15% compared to 0.3% in full-term births, and the etiology of this discrepancy remains unknown. The majority of NICU admissions receive potentially ototoxic aminoglycoside therapy, such as gentamicin, for presumed sepsis. Endotoxemia and inflammation are associated with increased cochlear uptake of aminoglycosides and potentiated ototoxicity in mice. We tested the hypothesis that sepsis or systemic inflammatory response syndrome (SIRS) and intravenous gentamicin exposure increases the risk of hearing loss in NICU admissions. MethodsThe Institutional Review Board at Oregon Health & Science University (OHSU) approved this study design. Two hundred and eight infants met initial criteria, and written, informed consent were obtained from parents or guardians of 103 subjects ultimately enrolled in this study. Prospective data from 91 of the enrolled subjects at OHSU Doernbecher Children's Hospital Neonatal Care Center were processed. Distortion product otoacoustic emissions (DPOAEs; f2 frequency range: 2063–10,031Hz) were obtained prior to discharge to assess auditory performance. To pass the DPOAE screen, normal responses in >6 of 10 frequencies in both ears were required; otherwise the subject was considered a “referral” for a diagnostic hearing evaluation after discharge. Cumulative dosing data and diagnosis of neonatal sepsis or SIRS were obtained from OHSU's electronic health record system, and the data processed to obtain risk ratios. ResultsUsing these DPOAE screening criteria, 36 (39.5%) subjects would be referred. Seventy-four (81%) subjects had intravenous gentamicin exposure. Twenty (22%) had ≥4 days of gentamicin, and 71 (78%) had <4 days. The risk ratio (RR) of referral with ≥4 days of gentamicin was 1.92 (p=0.01). Eighteen subjects had sepsis or met neonatal SIRS criteria, 9 of whom had ≥5 days of gentamicin and a DPOAE referral risk ratio of 2.12 (p=0.02) compared to all other subjects. Combining subjects with either vancomycin or furosemide overlap with gentamicin treatment yielded an almost significant risk ratio (RR=1.77, p=0.05) compared to the rest of the cohort. ConclusionsWe report an increased risk of referral with DPOAE screening for those receiving ≥4 days of intravenous gentamicin administration that may contribute to the greater prevalence of hearing loss in NICU graduates. We propose an expanded prospective study to gather a larger cohort of subjects, identifying those with sepsis or neonatal SIRS, to increase the statistical power of this study design. Subsequent studies also need to obtain follow-up diagnostic audiological data to verify whether the outcomes of DPOAE screening, in addition to the standard AABR screen, is a reliable predictor of permanent hearing loss following gentamicin exposure in the NICU.

PD10-09 GENTAMICIN INTRAVESICAL INSTILLATIONS DECREASE SYMPTOMATIC URINARY TRACT INFECTIONS AND ORAL ANTIBIOTIC USE IN PATIENTS WITH NEUROGENIC BLADDER ON INTERMITTENT CATHETERIZATION

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Neurogenic Voiding Dysfunction II1 Apr 2015PD10-09 GENTAMICIN INTRAVESICAL INSTILLATIONS DECREASE SYMPTOMATIC URINARY TRACT INFECTIONS AND ORAL ANTIBIOTIC USE IN PATIENTS WITH NEUROGENIC BLADDER ON INTERMITTENT CATHETERIZATION Lindsey Cox, J. Quentin Clemens, and Anne Cameron Lindsey CoxLindsey Cox More articles by this author , J. Quentin ClemensJ. Quentin Clemens More articles by this author , and Anne CameronAnne Cameron More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.949AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recurrent urinary tract infections (UTIs) are a morbid and costly clinical problem in patients with neurogenic bladder (NGB). Strategies for preventing UTIs are lacking in evidence. The use of prophylactic bladder instillations is described in the literature, but only in small cohorts. Daily intravesical gentamicin instillations for the prevention of UTIs is a commonly used clinical strategy for NGB patients on intermittent catheterization (IC) in our institution. We sought to determine if gentamicin bladder instillations reduce the rate of symptomatic UTIs, the use of oral/intravenous antibiotics, and/or the frequency of telephone encounters with their treating urologist for this population. METHODS We queried an IRB approved institutional Neurogenic Bladder database to identify subjects. Inclusion criteria included NGB of any etiology on IC for the period 6 months before and 6 months after initiating prophylactic intravesical gentamicin instillations. Exclusion criteria included short-term instillations only, less than 6 months follow up, discontinuation of IC (>4 weeks of indwelling catheter or urinary diversion). Symptomatic UTIs were defined as a patient complaint of symptoms consistent with past UTIs and treatment with antibiotics. Significance testing was performed using McNemar's, Wilcoxon signed-rank tests to evaluate paired variables before and after gentamicin instillations RESULTS Of 50 subjects identified, 22 met inclusion criteria after chart review. Subjects had a median age of 37.5 years, 63.6% had a spinal cord injury, 13.6% have multiple sclerosis, with median time since injury/diagnosis of 14 years. Patients used less oral antibiotic prophylaxis after gentamicin instillations were initiated (p=0.0016) and had fewer symptomatic UTI's (3.6 vs 0.73 episodes, p<0.0001); courses of treatment oral antibiotics (3.8 vs 0.91, p<0.0001); and telephone encounters for UTI's (2.3 vs 0.45, p=0.0011). CONCLUSIONS Gentamicin bladder instillations significantly decrease symptomatic UTI episodes and oral antibiotic use in patients with NGB. Prospective, placebo-controlled, longer-term trials are needed to determine if this effect is generalizable. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e203-e204 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lindsey Cox More articles by this author J. Quentin Clemens More articles by this author Anne Cameron More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Histone deacetylase inhibitor, sodium butyrate, attenuates gentamicin-induced nephrotoxicity by increasing prohibitin protein expression in rats

The major purpose in our study was to investigate the effects of sodium butyrate (NaBu) on nephrotoxicity induced by gentamicin in rats and determine further whether the protective effect is mediated by modulation of prohibitin protein expression. Gentamicin was injected intraperitoneally (100mg/kg body weight) once daily for 8 days to induce nephrotoxicity. The effect of acute and chronic treatment of sodium butyrate on nephrotoxicity induced by gentamicin was assessed. Various doses of sodium butyrate (50, 100, 200mg/kg, i.p.) was administered 30min prior to the daily gentamicin injection. Histological analysis was used to evaluate the lesions in kidney after gentamicin administration. Expression of prohibitin was evaluated with immunohistochemical and western blot analysis. The present study demonstrated that gentamicin treatment for 8 consecutive days significantly increased in the levels of blood urea nitrogen, creatinine, kidney injury molecule (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) which indicated nephrotoxicity induced by gentamicin. In addition, chronic treatment with NaBu significantly attenuated gentamicin-induced nephrotoxicity by increasing activities of superoxide dismutase, catalase and reduced glutathione. Immunohistochemical studies in gentamicin-induced rats also demonstrated an increase in the levels of inducible prohibitin after treatment with sodium butyrate. Our results indicated that sodium butyrate, a histone deacetylase inhibitor, decreased gentamicin-induced nephrotoxicity by enhancing renal antioxidant enzymes activity and the expression of prohibitin protein.

Once versus Twice Daily Gentamicin Dosing for Infective Endocarditis: A Randomized Clinical Trial

Objectives: The aim of this randomized study was to investigate the effects of once versus twice daily gentamicin dosing on renal function and measures of infectious disease in a population with infective endocarditis (IE). Methods: Seventy-one IE patients needing gentamicin treatment according to guidelines were randomized to either once (n = 37) or twice daily (n = 34) doses of gentamicin. Kidney function (glomerular filtration rate, GFR) was measured with an isotope method (⁵¹Cr-EDTA) at the beginning of treatment and at discharge. Treatment efficacy was assessed by C-reactive protein (CRP) time to half-life, mean CRP and leukocytes. Results: Baseline GFR was similar in the two groups. Both groups displayed a significant fall in GFR from admission to discharge. The mean decrease in GFR was as follows: with once daily gentamicin, 17.0% (95% confidence interval 7.5–26.5), and with twice daily gentamicin, 20.4% (95% confidence interval 12.0–28.8). However, there was no significant difference in the GFR decrease between the once and twice daily regimens (p = 0.573). No difference in infection parameters was demonstrated between the two dosing regimens. Conclusions: A twice daily gentamicin dosing regimen is neither less nephrotoxic nor more efficient than a once daily regimen in the treatment of IE patients. When indicated, gentamicin may therefore also be administered as a single-dose regimen in the treatment of IE patients.